Parkinson's disease (PD) is the second most common neurodegenerative disease, following Alzheimer's disease. PD is characterized by motor symptoms including tremor, rigidity, bradykinesia, and postural instability. Pathological studies have observed a loss of dopaminergic neurons in the substantia nigra (SN) along with the presence of α-synuclein-rich cytoplasmic inclusions in the remaining neurons (Spillantini et al., 1997).

L-3,4-dihydroxyphenylalanin (L-DOPA) is the most effective drug in dopamine replacement therapy; however, long-term L-DOPA therapy can lead to choreiform involuntary movement known as L-DOPA-induced dyskinesia (LID). LID is one of the most disabling complications for patients with PD, developing in approximately 50 % of those treated with L-DOPA for five years (Holloway et al., 2004; Rascol et al., 2000; Stocchi et al., 2010), and eventually affecting 90 % of patients during prolonged L-DOPA therapy (Grandas et al., 1999).

Animal studies investigating the pathophysiology of LID have primarily utilized 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned nonhuman primates or 6-hydroxydopamine (6-OHDA)-lesioned rodent models (Cenci and Crossman, 2018; Cesaroni et al., 2022). LID is well-established in rodents lesioned with 6-OHDA targeting the SN, medial forebrain bundle (MFB), or striatum. However, the 6-OHDA-lesioned model replicates dopaminergic neuron loss but does not exhibit α-synuclein aggregation or the formation of α-synuclein-rich cytoplasmic inclusions, which are the characteristic findings of PD pathology (Lindgren et al., 2012).

A new rodent model induced by overexpression of α-synuclein using adeno-associated virus (AAV) vector was recently introduced (Decressac et al., 2012a; Decressac et al., 2012b; Oliveras-Salva et al., 2013; Van der Perren et al., 2015). Transduction of the α-synuclein gene via the AAV vector into the nigral dopaminergic neuron successfully resulted in dopaminergic neuron loss, α-synuclein aggregation in the remnant neuron, and hemiparkinsonism in behavioral tests. Since the pathological changes and behavioral impairments are progressive, this model is considered to more closely reflect the pathological condition of human PD.

Evidence suggests that changes in activity of neurotransmitters (Carta et al., 2007; Cenci, 2014; Lee et al., 2015; Politis et al., 2014; Roussakis et al., 2016), as well as neuroinflammation associated with α-synuclein (Pisanu et al., 2018; Tansey et al., 2022), also play important roles in both PD and LID. Therefore, this AAV vector-mediated model could be a valuable tool for further research into LID that reflects α-synuclein pathology. In this study, we generated parkinsonian mice using human α-synuclein-encoding recombinant AAV2/7 vector and administered L-DOPA to induce LID. We also conducted histologic analyses to evaluate changes in the dopaminergic system and their association with LID.